Age-related impairment of conducted dilation in human coronary arterioles
Age-related impairment of conducted dilation in human coronary arterioles
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DOI：
10.1152/ajpheart.00179.2014
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发表时间：
2014-06-15
影响因子：
4.8
通讯作者：
Bagi, Zsolt
中科院分区：
文献类型：
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作者：
Feher, Attila;Broskova, Zuzana;Bagi, Zsolt
传导性血管舒张对于协调沿着距离的血管阻力以确保充分的组织灌注至关重要。我们假设冠状动脉阻力血管的传导性舒张随年龄增长而下降。从心脏手术患者（n = 27）的右心耳分离冠状小动脉。对小动脉（类似于100 μ m）进行插管和加压（80 mmHg），并产生自发性肌源性张力。通过局部施用从玻璃微量移液管（类似于3 μ m尖端开口，定位在靠近血管壁处）喷射的内皮依赖性激动剂缓激肽（BK; 100 μ M）来启动传导血管舒张。直径的变化进行了测量，在当地和上游网站（500和1,000 μ m的刺激）与视频显微镜。BK局部给药引起血管舒张，其幅度随刺激持续时间增加（1、3和5 x 100 ms后分别为69 +/- 6、81 +/- 6、90 +/-2%）。BK诱导的扩张在上游部位仍然很大（500 μ m：53 +/- 7%; 1，000 μ m：46 +/- 9%）。差距连接解偶联剂甘珀酸或18-α-大黄酸不影响局部反应，但减少了传导性血管舒张。小/中电导钙激活钾通道（SKCa/IKCa）抑制剂apamin和TRAM 34可减少局部和远端部位的扩张。我们发现，老年患者（≥ 64岁）的传导性扩张明显减少，但局部反应没有明显减少。一氧化氮（NO）合成抑制剂N-ω-硝基-L-精氨酸甲酯不影响局部反应，但明显减少年轻（
Conducted vasodilation is essential to coordinate vascular resistance along distances to ensure adequate tissue perfusion. We hypothesized that conducted vasodilation of coronary resistance arteries declines with age. Coronary arterioles were dissected from right atrial appendage of patients (n = 27) undergoing cardiac surgery. Arterioles (similar to 100 mu m) were cannulated and pressurized (80 mmHg), and developed spontaneous myogenic tone. Conducted vasodilation was initiated by locally administering the endothelium-dependent agonist bradykinin (BK; 100 mu M) ejected from a glass micropipette (similar to 3 mu m tip opening, positioned in close proximity to the vessel wall). Diameter changes were measured at local and upstream sites (500 and 1,000 mu m from the stimulus) with videomicroscopy. Local administration of BK elicited vasodilation, the magnitude of which increased with the duration of stimulus (69 +/- 6, 81 +/- 6, 90 +/- 2%, after 1, 3, and 5 x 100 ms, respectively). BK-induced dilation remained substantial at upstream sites (500 mu m: 53 +/- 7%; 1,000 mu m: 46 +/- 9%). The gap junction uncoupler carbenoxolone or 18-alpha-glycyrrhetinic acid did not affect local responses, but diminished conducted vasodilation. Inhibitors of small/intermediate conductance calcium-activated potassium channels (SKCa/IKCa), apamin and TRAM34, reduced dilations both at local and remote sites. We found that conducted dilation, but not the local response, was significantly reduced in older (>= 64 yr) patients. The nitric oxide (NO) synthesis inhibitor N-omega-nitro-L-arginine methyl ester did not affect local responses, but markedly reduced conducted dilation in younger (